Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans
| Autor: | Ingiäld Hafström, Suzanne Lind, Mats Eriksson, Robert J. Konrad, Maria Dahlin, Mats Rudling, Guoqing Cao, Per Åmark, Lars Ståhle, Lena Persson, Cecilia Gälman, Håkan Wallén, Beatrice G. Sjöberg, Bo Angelin, Jason S. Troutt |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty genetic structures Cholestyramine Resin Down-Regulation Lathosterol Biology chemistry.chemical_compound Internal medicine medicine Atorvastatin Humans Pyrroles Sweden Cholestyramine Cross-Over Studies Cholesterol Human Growth Hormone PCSK9 Anticholesteremic Agents Serine Endopeptidases Cholesterol LDL Fasting Circadian Rhythm Endocrinology chemistry Liver Receptors LDL Heptanoic Acids Low-density lipoprotein LDL receptor Kexin lipids (amino acids peptides and proteins) Female Proprotein Convertases Hydroxymethylglutaryl-CoA Reductase Inhibitors Proprotein Convertase 9 Cardiology and Cardiovascular Medicine Diet Ketogenic Energy Intake medicine.drug Lipoprotein |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 30(12) |
| ISSN: | 1524-4636 |
| Popis: | Objective— To gain insight into the function of proprotein convertase subtilisin kexin type 9 (PCSK9) in humans by establishing whether circulating levels are influenced by diurnal, dietary, and hormonal changes. Methods and Results— We monitored circulating PCSK9 in a set of dynamic human experiments and could show that serum PCSK9 levels display a diurnal rhythm that closely parallels that of cholesterol synthesis, measured as serum lathosterol. In contrast to these marked diurnal changes in cholesterol metabolism, serum low-density lipoprotein (LDL) cholesterol levels remained stable during the diurnal cycle. Depletion of liver cholesterol by treatment with the bile acid–binding resin, cholestyramine, abolished the diurnal rhythms of both PCSK9 and lathosterol. Fasting (>18 hours) strongly reduced circulating PCSK9 and lathosterol levels, whereas serum LDL levels remained unchanged. Growth hormone, known to be increased during fasting in humans, reduced circulating PCSK9 in parallel to LDL cholesterol levels. Conclusion— Throughout the day, and in response to fasting and cholesterol depletion, circulating PCSK9 displays marked variation, presumably related to oscillations in hepatic cholesterol that modify its activity in parallel with cholesterol synthesis. In addition to this sterol-mediated regulation, additional effects on LDL receptors may be mediated by hormones directly influencing PCSK9. |
| Databáze: | OpenAIRE |
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